Patent GB-736818-A (GB)
Title: Improvements in or relating to preparation of 3-keto steroids having cis junction of rings a and b
IPC: C07J9/00
Filed: 1952-12-18
Abstract: The invention comprises D 7-pregnene-3,20-dione, 3 - keto - bisnor - D 7 - cholenic acid and esters thereof, and a process for reducing the 4-5 double bond of a 3-keto-D 4-steroid (excluding steroids containing an 11-keto group) by means of hydrogen in the presence of palladium catalyst and an inorganic base in an anhydrous medium to form a 3-keto-A/B-cissteroid substantially free of the allo isomer. The reduction may be effected at pressures below 5 lb. per sq. in. and/or at a temperature below 50 DEG  C., or at atmospheric pressure and at a temperature from about 20 DEG  to about 30 DEG  C.  The 3-keto group in the D 4-steroid reactant may be the sole keto group attached to the nucleus of the reactant.  The reactant may be a pregnene, a sterone such as cholesterone or stigmastenone, a steroid of the C17 or C22 series or a steroid containing a double bond in the 7(8) position such as D 4.7-pregnadiene-dione-3,20 and the 20-cyclic ketal derivatives thereof derived from alkylene glycols.  Suitable inorganic bases are caustic alkalis, alkali metal carbonates, alkali metal phosphates such as sodium tetraphosphate and potassium pyrophosphate.  The concentration of the inorganic base may be about 20 per cent by weight of the 3-keto-D 4-steroid reactant used.  A temperature below 50 DEG  C. and a pressure below 5 pounds per square inch are suitable for the hydrogenation.  In the examples pregnan-3,20-dione is prepared from progesterone, D 7-pregnene-dione-3,20 and the 20-cyclic ethylene ketal derivative are prepared from 7-dehydroprogesterone and the 20-cyclic ethylene ketal derivative respectively (the ketal product may be hydrolysed with sulphuric acid in methanol to form D 7-pregnene - dione - 3,20), coproergost - 22(23)-ene-3-one is prepared from isoergosterone, methyl 3 - keto - bisnor - 7 p  - cholenate is prepared from methyl 3 - keto - bisnor - 4,7-choladienate, methyl 3 - keto - bisnor - cholanate is prepared from methyl 3-keto-bisnor-4-cholenate, etiochola - 3,17 - dione - 17 - ethylene ketal is prepared from 4-androstene-3,17-dione-17-ethylene ketal (the ketal product may be hydrolysed with sulphuric acid in methanol to form etiocholan-3a -ol-17-one), and 5-isostigmast-22-ene-3-one is prepared from stigmastadienone.  In the above examples esters other than the methyl ester may be used, e.g. the ethyl or butyl ester or an ester containing the benzoyl, hemisuccinoyl or naphthoyl group, and cyclic ketals other than the ethylene ketal may be used, e.g. ketals containing 3 or 4 carbon atoms in the cyclic ring.  It is stated also that D 7,9,(11) - pregnadiene - 3,20 - dione may be prepared from D 4,7,9(11)-pregnatrien-3,20-dione and methyl 3-keto-D 7,9(11)-choladienate may be prepared from methyl 3-keto-D 4,7,9(11)-cholatrienate by the above reduction process.  Methyl 3 - keto - bisnor - 4,7 - choladienate is prepared by oxidizing methyl 3b -hydroxybisnor-5,7-choladienate with cyclohexanone and aluminium isopropylate.  Methyl 3-keto-bisnor-4-cholenate, 4 - androstene - 3,17 - dione - 17 - ethylene ketal and stigmastadienone are prepared by a similar method.  17 - Ethylene ketal of dehydroandrosterone is prepared by refluxing dehydroandrosterone and ethylene glycol in the presence of p-tosyl acid monohydrate.  3a  - Acetoxybisnorlithocholic acid is prepared by the ozonolysis of 5-isostigmasten-3a -ol acetate. Specification 736,817 is referred to.